Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.

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title = "Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.",
abstract = "Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a {"}vascular disease-like{"} phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.",
author = "Lisa Berglund and Valeriya Lyssenko and Claes Ladenvall and Olga Kotova and Andreas Edsfeldt and Kasper Pilgaard and Sami Alkayyali and Charlotte Br{\o}ns and Carol Forsblom and Anna Jonsson and Anna Zetterqvist and Mihaela Nitulescu and {Ruiz McDavitt}, Christian and Pontus Dun{\'e}r and Alena Stanc{\'a}kov{\'a} and Johanna Kuusisto and Emma Ahlqvist and Maria Lajer and Lise Tarnow and Sten Madsbad and Peter Rossing and Kieffer, {Timothy J} and Olle Melander and Marju Orho-Melander and Peter Nilsson and Per-Henrik Groop and Allan Vaag and Bengt Lindblad and Anders Gotts{\"a}ter and Markku Laakso and Isabel Goncalves and Leif Groop and Maria Gomez",
year = "2016",
doi = "10.2337/db15-0122",
language = "English",
volume = "65",
pages = "239--254",
journal = "Diabetes",
issn = "1939-327X",
publisher = "American Diabetes Association Inc.",
number = "1",